Virus-like particles (VLPs), which resemble in size and morphology true capsids but do not incorporate viral genetic material, are attractive vaccine candidates because they are non-infectious, they have the safety profile of subunit vaccines, but have superior immunological properties. See Grgacic et al., 40 METHODS 60-5 (2006). The particulate nature of VLPs, especially those in the size range of 40-50 nm (Fifis et al., 173 J. IMMUNOL. 3148-54 (2004), allows efficient uptake by dendritic cells (DCs), central players in initiation of the innate and adaptive immune response. VLPs can stimulate maturation of DCs, induce upregulation of major histocompatability complexes (MHC) and costimulatory molecules, and lead to production of cytokines. VLPs also serve as their own adjuvant, eliciting “danger signals,” often through stimulation via Toll-like receptors. As exogenous antigens, VLPs are processed and presented by MHC class II, but they can also be taken up and processed via the MHC class I pathway by cross presentation. See Dickgreber et al., 182 J. IMMUNOL. 1260-69 (2009).
In order to expand the application of VLPs as vaccines, efforts have been made to devise chimeric VLPs that present epitopes of proteins that cannot self assemble. See Boisgérault et al., 1 EXPERT REV. VACCINES 101-09 (2002). The most common way in which this has been achieved is to construct fusions proteins of a VLP protein and a candidate vaccine peptide. Despite the described successes of this approach, there are limitations to the size and nature of epitopes that can be inserted into VLPs. Novel approaches for the generation of potent VLP vaccines are greatly needed.